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George Cotsarelis, M.D.
Albert M. Kligman Associate Professor


M8 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104

Tel: 610-902-2400 (Patient Appointments)

 
 
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Education
1983        B.A.        University of Pennsylvania
1987        M.D.        University of Pennsylvania Medical School

Clinical Specialties
Hair and Scalp disorders

Research Area of Interest
Epithelial Stem Cells
Hair Follicle Biology
Cutaneous Gene Therapy
Epithelial Carcinogenesis
Wound Healing

Basic Science Research Summary

1. Epithelial Stem Cells: A major goal of my laboratory is to identify genes controlling epithelial stem cells. We originally localized cutaneous epithelial stem cells to an area of the hair follicle called the bulge in both mouse and human skin. Using expression cloning, we identified keratin 15 (K15) as a marker for bulge cells. K15 is an intermediate filament protein that is preferentially expressed at high levels in bulge cells. We then isolated the K15 promoter. Keratin promoters are powerful tools for studying skin biology that have lead to an improved understanding of the genetic regulation of hair growth and development, as well as cutaneous carcinogenesis. The K15 promoter targets epithelial stem cells and will be valuable for studying the role of bulge cells in alopecia and carcinogenesis.

We are currently targeting several different genes to the bulge cells of transgenic mice using the K15 promoter to address the role of different oncogenes in tumorigenesis and alopecia. Using Real Time PCR, microarray analysis, laser capture microdissection, and a host of other conventional molecular techniques, we are studying the role of novel and known genes in hair follicle cycling and cutaneous biology.

2. Cutaneous Gene Therapy: We have developed a means for introducing plasmid DNA into human hair follicle progenitor cells by applying a mixture of DNA and liposomes topically to human skin transplanted to immunodeficient (scid) mice. The long-term goals of this project are to treat disorders of the skin and hair using this approach.

3. Carcinogenesis: Since epithelial stem cells rarely proliferate and are present throughout the lifetime of the individual, they may be susceptible to accumulating DNA damage, which can result in tumor formation. We are currently studying the role of epithelial stem cells in tumors of the skin as well as other epithelial tissues, such as in the eye and gastrointestinal tract.

Dr. Cotsarelis' Lab Personnel:
Ito, Mayumi, Ph.D.: Post Doctoral Fellow
Kira, Masahiro, M.D., Ph.D.: Visiting Scientist
Yang, Zai-Xin: Research Specialist
Garza, Luis: Post Doctoral Fellow
Cui, Chunhua: Research Associate


Selected Publications

  1. Morris, R., Liu, Y., Marles, L., Yang, Z., Trempus, C., Li, S., Lin, J., Sawicki, J., Cotsarelis, G. Capturing and profiling hair follicle stem cells. Nature Biotechnology 22:411-417, 2004.

  2. Liu, Y., Lyle, S. Solky, B, Cotsarelis, G. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J Invest Dermatol 121:985-988, 2003.

  3. Kantor J, Jay L, Brooks D, Cotsarelis G. Decreased Serum Ferritin is Associated with Alopecia in Women. J Invest Dermatol 121:963-968, 2003.

  4. Xu, X. Lyle, S. Liu, Y. Solky, B. Cotsarelis G. Differential expression of cyclin D1 in the human hair follicle. Am J Pathol 163:969-78, 2003.

  5. Xu, X, Solky, B, Elenitsas, R, Cotsarelis, G. Scarring alopecia associated with mastocytosis J Cutaneous Pathology 30: 561-565, 2003.

  6. Wu, H, Stanley, JR, Cotsarelis, G. Desmoglein isotype expression in the hair follicle and its cysts correlates with type of keratinization and degree of differentiation. J Invest Dermatol 120:1052-1057, 2003.

  7. Miller J, Djabali K, Chen, T, Ioffreda M, Lyle S, Christiano A, Holick M, Cotsarelis G. Atrichia caused by mutations in the vitamin D receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene. J Invest Dermatol, 117 612-617 (2001).

  8. Cotsarelis, G., and Millar, S. Towards a molecular understanding of hair loss and its treatment. Trends in Molecular Medicine. 7: 293-301 (2001) .

  9. Domashenko A, Gupta S, Cotsarelis G. Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex. Nature Biotechnology, 18: 420-423 (2000).

  10. Paus, R., and Cotsarelis, G. The biology of hair follicles. N Engl J Med. 341: 491-497 (1999).

  11. Jih, D, Lyle, S, Elenitsas, R, Elder, D, Cotsarelis, G. Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells. J Cutaneous Pathology. 26: 113-118, (1999)

  12. Lyle, S, Christofidou-Solomidou, M. Liu, Y, Elder, D, Albelda, S., Cotsarelis, G. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Science. 111: 3179-3188 (1998).

  13. Cotsarelis, G., Sun, T, Lavker, R. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 61: 1329-1337, 1990.

Links of Interest